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. 2022 Sep 5;7:52. doi: 10.1038/s41525-022-00324-x

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — a Increased IL10RB expression is associated with worse COVID-19 outcomes in vivo. *, **, and *** for FDR-adjusted p (FDR) ≤ 0.05, 0.01, and 0.001, respectively. Error bars show 95% CI. b In vitro experimental overview. c CRISPRa gRNAs (IL10RB-1, IL10RB-2, IL10RB-3, and IL10RB-4) were used to overexpress IL10RB in hiPSC-derived NGN2-glutamatergic neurons. ***, **, and * correspond to p-values from the linear model of equal or less than 0.001, 0.01, and 0.05, respectively. For the SARS-CoV-2 viral load (right panel) we performed pairwise comparison with unpaired t-test; ***, **, and * correspond to p values equal to, or less than, 0.001, 0.01, and 0.05, respectively. d Competitive gene set enrichment analysis in hiPSC-derived NGN2 glutamatergic neurons. Each row represents a different experimental condition and each column a different gene set; the top row shows the effect of SARS-CoV-2 infection, while the remaining rows show the effect of gene manipulation (e.g., IL10RB vs. nontargeting siRNA) within a specific group (e.g., CoV(−): uninfected cells). The left side of the plot (Gene ontology gene sets; white background) indicates enrichment for canonical pathways and biological processes that are significantly enriched (FDR < 0.05) in SARS-CoV-2 infection (top row), while the right side (Betacoronavirus Gene sets; gray background) illustrates enrichment for gene sets that correspond to betacoronavirus infections across different cell systems²¹ (only significant results are shown; FDR < 0.05).